TBK1/IKKε-IN-4 is a novel and potent TBK1 and IKKε inhibitor with anticancer activity. It inhibits TBK1 and IKKε with IC50 of 13 nM and 59 nM, respectively.
Physicochemical Properties
| Molecular Formula | C28H35N7O4 |
| Molecular Weight | 533.62 |
| Exact Mass | 533.275 |
| CAS # | 1381930-17-1 |
| PubChem CID | 121230617 |
| Appearance | White to light yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 668.1±65.0 °C at 760 mmHg |
| Flash Point | 357.9±34.3 °C |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.633 |
| LogP | 2.85 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 39 |
| Complexity | 722 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | PVQUVXVUIZZLMP-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C28H35N7O4/c1-33-11-13-34(14-12-33)10-5-15-39-25-17-21(16-24(37-3)26(25)38-4)31-28-29-18-20-19-30-35(27(20)32-28)22-6-8-23(36-2)9-7-22/h6-9,16-19H,5,10-15H2,1-4H3,(H,29,31,32) |
| Chemical Name | N-[3,4-dimethoxy-5-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]-1-(4-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-6-amine |
| Synonyms | TBK1/IKKεIN4 TBK1/IKKε IN 4 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Treatment with TBK1/IKKε-IN-4 (Compound II; 96 hours; A549 and HCC44 cells) exhibits selective toxicity in TBK1-dependent cancer cell lines (IC50 of approximately 0.4 µM for A549 cells and approximately 4.2 µM for H441 cells)[1]. The AKT activity is inhibited by TBK1/IKKε-IN-4 (Compound II; 0-2 µM; 30 minutes; HCC44 cells) treatment[1]. The LPS-induced production of IFNβ (IC50 = 62 nM) and its target genes, IP10 (IC50 = 78 nM) and Mx1 (IC50 = 20 nM), is inhibited by TBK1/IKKε-IN-4 (Compound II). At dosages up to 20 µM, TBK1/IKKε-IN-4 does not affect TNFR1-dependent p65 NFκB nuclear translocation, but it efficiently inhibits TLR3-dependent IRF3 nuclear translocation in cells with an IC50 under 100 nM[1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: HCC44 cells Tested Concentrations: 0 µM, 0.5 µM, 1 µM, 2 µM Incubation Duration: 30 minutes Experimental Results: Was sufficient to blunt baseline AKT activity. |
| References |
[1]. TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation. Mol Cell. 2011 Feb 18;41(4):458-70. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~70 mg/mL (~131.18 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.75 mg/mL (8.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 47.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 3.5 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 3.5 mg/mL (6.56 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8740 mL | 9.3700 mL | 18.7399 mL | |
| 5 mM | 0.3748 mL | 1.8740 mL | 3.7480 mL | |
| 10 mM | 0.1874 mL | 0.9370 mL | 1.8740 mL |